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Gut Microbes Linked to Rheumatoid Arthritis

The presence of a specific type of gut bacteria correlates with rheumatoid arthritis in newly diagnosed, untreated people. The finding suggests a potential role for the bacteria in this autoimmune disease.

Rheumatoid arthritis is a chronic inflammatory disorder that can cause pain, swelling, stiffness, and loss of function in the finger, wrist, and other joints throughout the body. It occurs when the immune system mistakenly attacks the body’s own tissue, such as the membranes that line the joints.

The causes of rheumatoid arthritis aren’t completely known. Genes tied to the immune system may contribute. Environmental factors, such as cigarette smoking, diet and stress, may also play a role in triggering the disease. Treatments include medications to relieve pain and reduce inflammation.

The immune system is influenced by the microbiome, a network of microorganisms that live in and on the human body. These microbes outnumber the body’s cells by 10 to 1. Trillions of microbes — both helpful and harmful — reside in the digestive tract. The gut microbiome has been linked to arthritis in animal studies.

To see if these microbes might also be associated with rheumatoid arthritis in humans, Dr. Dan Littman of NYU School of Medicine led a team of researchers that examined DNA in 114 stool samples from both healthy people and those who had rheumatoid or psoriatic arthritis. The team identified gut bacteria by extracting DNA from the samples and then analyzing a bacteria-specific gene called the 16S ribosomal RNA gene. The research was funded in part by NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Allergy and Infectious Diseases (NIAID), and National Human Genome Research Institute (NHGRI). Results appeared online on November 5, 2013, in eLife.

The researchers found that 75% of people with new-onset, untreated rheumatoid arthritis had the bacterium Prevotella copri in their intestinal microbiome. In comparison, it was present in 12% of people with chronic, treated rheumatoid arthritis, 38% of people with psoriatic arthritis, and 21% of those in the control group. Increased levels of P. copri correlated with reductions in several groups of beneficial microbes, such as Bacteroides. The researchers performed more complete DNA sequencing on a subset of samples and identified unique Prevotella genes that correlated with rheumatoid arthritis.

To test whether P. copri could influence inflammation, the team administered the bacteria to healthy mice so that the bacteria became part of their gut microbiome.Mice were then given a chemical that inducedcolitis, a model of gut inflammation. Animals with P. copri developed more severe symptoms than the mice that hadn’t received the bacteria. The finding provides further evidence for a potential role for P. copri in inflammation.

“Our own results in mouse studies encouraged us to take a closer look at patients with rheumatoid arthritis, and we found this remarkable and surprising association,” Littman says. “At this stage, however, we cannot conclude that there is a causal link between the abundance of P. copri and the onset of rheumatoid arthritis. We are developing new tools that will hopefully allow us to ask if this is indeed the case.”

Funding: NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Allergy and Infectious Diseases (NIAID), and National Human Genome Research Institute (NHGRI); Howard Hughes Medical Institute; American Gastroenterological Association; National Science Foundation; and Danone Research.